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New allergy-driving T cell; an eye-on-a-chip; hepatitis B in shrews

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New allergy-driving T cell; an eye-on-a-chip; hepatitis B in shrews

This is a recurring column on early-stage research in animals or other laboratory models that has not entered the clinic yet but could have implications for future research and development of human medicines.

New immune cell subtype in mice with allergies

Scientists have identified a subtype of T cells that may drive allergic disease and life-threatening allergic reactions like anaphylaxis.

In the study funded by the U.S. National Institute of Allergy and Infectious Diseases, researchers at Yale University, the Jackson Laboratory for Genomic Medicine and other institutes bred mice to have DOCK8 deficiency, which in humans causes severe allergies and asthma, as well as recurrent viral infections. According to the researchers' observations, the DOCK8-deficient mice had certain T follicular helper cells, called Tfh13 cells, not found in normal mice.

Normal mice were then exposed to and made sensitive to respiratory and food allergens, inducing severe allergic reactions leading to anaphylaxis, which results in constriction of the airways and sudden drop in blood pressure. The allergic mice were found to have Tfh13 cells and high-affinity immunoglobulin E, or IgE, antibodies, which bind to allergens and cause allergic reactions.

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Allergic mice were found to have certain T cells not previously identified in humans, according to an NIH-funded study.

Source: Associated Press

When the researchers prevented Tfh13 cell development in allergic mice, the animal models did not produce anaphylactic IgE.

The scientists then studied blood samples from humans with peanut or respiratory allergies and non-allergic humans, and found that allergic individuals had higher levels of Tfh13 cells.

According to the scientists, targeting Tfh13 cells may aid in preventing an anaphylaxis allergic reaction.

An 'eye-on-a-chip'

An eye-on-a-chip model could be used as an accurate substitute for the human eye in drug development for ophthalmic conditions such as dry eye disease, research from University of Pennsylvania showed.

The artificial human eye replica was engineered to imitate a healthy eye and an eye with dry eye disease, a common condition in older adults that occurs when an individual does not have enough tears to lubricate the eye. The eye-on-a-chip was constructed to imitate the eye's biology, down to the rate of blinking and spread of tear secretions over the eye.

The dry eye disease model involved cutting the blinking rate in half and creating an enclosed environment that simulated real-life conditions.

According to clinical tests, both the healthy and dry eye disease eye-on-a-chip models replicated the performance of human eyes in liquid production, tear film salt content and time to break up a tear film.

The UPenn investigators then used the eye-on-a-chip device to test a dry eye disease drug candidate, Novartis AG's lubricin-based drug licensed from Lubris BioPharma, LLC.

"When we tested this drug in our device, we were able to demonstrate its friction-lowering effects, but, more importantly, using this model we discovered its previously unknown capacity to suppress inflammation of the ocular surface," said Dan Huh, co-leader of the study and UPenn associate professor.

According to Huh and fellow study leader, UPenn graduate student Jeongyun Seo, comparing the healthy, diseased, and diseased and treated eye-on-a-chip models further revealed the lubricin drug's efficacy and how it works.

Only one U.S. Food and Drug Administration-approved drug treats dry eye disease, Takeda Pharmaceutical Company Ltd.'s Xiidra, which was sold to Novartis in July.

Seo noted the possibility of using the eye-on-a-chip for testing contact lenses and eye surgeries in addition to drug development.

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New strain of hepatitis B virus in shrews

Scientists in Germany may have identified a better animal model for hepatitis B research, as an unusual strain of the virus was discovered in shrews, small mole-like mammals.

Hepatitis B, which affects hundreds of millions of people worldwide, becomes chronic when a certain immunomodulator protein, called hepatitis B e-antigen, or HBeAg, forms during infection, suppressing the body's immune response.

According to researchers at the University Medicine Berlin and German Center for Infection Research, or DZIF, all known chronic hepatitis B in mammals is characterized as such. However, in nearly 700 shrew samples from Europe and Africa, HBeAg was noticeably absent, despite high levels of hepatitis B virus in their blood.

The scientists said the missing HBeAg means the virus takes an unknown path into shrews' liver cells.

"We still do not know all HBV receptor molecules," said Jan Felix Drexler, a DZIF scientist.

Researchers plan to further study the infection's path without the presence of HBeAg.

"Shrews could be a promising animal model for HBV research," Drexler concluded.